gamma-Crystallins are associated with cataract in both human and animal models. They may also have stress related roles in other eye tissues, notably retina. We have shown that they can play a role in stabilization of cytoskeleton in lens. g-Crystallins have highly unusual solution properties that fit them for high protein concentration environments. They have stable, tightly folded structures but can unfold to form amyloid like fibrils. We have studied unfolding/refolding in members of the gS-crystallin family from birds and mammals. A single amino acid residue which differs between birds and mammals appears to have a key role in determining long term stability of the protein fold and the ability of the protein to adopt an alternative conformation which seems to resist formation of light scattering aggregates. We have be able to crystallize chicken gS-crystallin, which is significant since mammalian orthologs have previously proved to be resistant to crystallization. This may reflect a major difference in intramolecular interactions perhaps involved in preventing aggregation in mammalian lenses. X-ray analysis is underway. We are also working on a variant of mouse gS and on refolded proteins that may show conformational variation that could help to illuminate the folding pathways of this family with its important role in lens transparency.